口腔白斑和鳞癌中p16基因甲基化的研究

The p16 methylation in oral leukoplakia and oral squamous cell carcinoma

目的 探讨p16基因甲基化在口腔黏膜白斑癌变中的作用。方法 采用甲基特异性PCR技术检测了 10例正常口腔黏膜、20例白斑上皮单纯增生、11例白斑上皮轻度异常增生、10例白斑上皮中度异常增生、9例白斑上皮重度异常增生、10例鳞癌Ⅰ级、12例鳞癌Ⅱ级、8例鳞癌Ⅲ级标本的p16基因甲基化情况。结果 上述各组的p16基因甲基化率分别为 0、5%、18%、10%、22%、50%、42%和 63%。p16基因甲基化率与口腔黏膜组织恶性度显著正相关,并与p16蛋白缺失表达率呈显著正相关关系(rp=0 777 , rs=0 960, P<0 001)。结论 p16基因甲基化状态可作为白斑癌变和口腔鳞癌诊断的分子生物学重要标志之一。

Objective To investigate p16 gene methylation in normal mucosa, leukoplakia with hyperplasia and dysplasia and oral squamous cell carcinoma.Methods 20 patients of leukoplakia with hyperplasia, 11 patients of leukoplakia with mild dysplasia, 10 patients of leukoplakia with moderate dysplasia, 9 patients of leukoplakia with severe dysplasia, 10 patients with OSCC in low grade, 12 patients with OSCC in moderate grade, 8 patients with OSCC in high grade, and 10 normal individuals were studied on p16 methylation. Results Rates of p16 methylation were 0 for normal individuals, 5% for patients of leukoplakia with hyperplasia, 18% for patients of leukoplakia with mild dysplasia, 10% for patients of leukoplakia with moderate dysplasia, 22% for patients of leukoplakia with moderate dysplasia, and 50% for patients with OSCC in low grade, 42% for patients with OSCC in moderate grade, and 63% for patients with OSCC in high grade. Rates of p16 methylation increased with tissue malignance increase and correlated positively to the tissue malignance. The rate (82%) of p16 methylation in OSCC patients with lymph node metastasis was significantly high than that (32%) of OSCC patients without lymph nodes metastasis. The methylated rates of p16 correlated positively to the lacking rates of p16 protein. Conclusions It was first reported that p16 methylation occurred in every stage of leukoplakia cancerization and OSCC progression. p16 can be one of the important molecular biological markers for leukoplakia cancerization and OSCC progression. p16 methylation is recommended as an important marker for diagnosis of OSCC.